他汀类药物的使用与胆结石疾病继发胆囊切除术的风险。

Statin use and risk of gallstone disease followed by cholecystectomy.

作者信息

Bodmer Michael, Brauchli Yolanda B, Krähenbühl Stephan, Jick Susan S, Meier Christoph R

机构信息

Division of Clinical Pharmacology and Toxicology, University Hospital, Basel, Switzerland.

出版信息

JAMA. 2009 Nov 11;302(18):2001-7. doi: 10.1001/jama.2009.1601.

DOI:10.1001/jama.2009.1601

PMID:19903921

Abstract

CONTEXT

Gallstone disease is a leading cause of morbidity in western countries and carries a high economic burden. Statins decrease hepatic cholesterol biosynthesis and may therefore lower the risk of cholesterol gallstones by reducing the cholesterol concentration in the bile. Data on this association in humans are scarce.

OBJECTIVE

To study the association between the use of statins, fibrates, or other lipid-lowering agents and the risk of incident gallstone disease followed by cholecystectomy.

DESIGN, SETTING, AND PARTICIPANTS: Case-control analysis using the UK-based General Practice Research Database. Incident patients between 1994 and 2008 and 4 controls per each patient were identified and matched on age, sex, general practice, calendar time, and years of history in the database. The study population was 76% women and the mean (SD) age was 53.4 (15.0) years at the index date. Conditional logistic regression was used to estimate the odds ratio (OR) of developing gallstones followed by cholecystectomy in relation to exposure to lipid-lowering agents, stratified by exposure timing and duration. The ORs and 95% confidence intervals (CIs) were adjusted for smoking, body mass index, ischemic heart disease, stroke, and estrogen use.

MAIN OUTCOME MEASURE

The adjusted OR (AOR) for developing gallstone disease followed by cholecystectomy in relation to exposure to lipid-lowering agents.

RESULTS

A total of 27,035 patients with cholecystectomy and 106,531 matched controls were identified, including 2396 patients and 8868 controls who had statin use. Compared with nonuse, current statin use (last prescription recorded within 90 days before the first-time diagnosis of the disease) was 1.0% for patients and 0.8% for controls (AOR, 1.10; 95% CI, 0.95-1.27) for 1 to 4 prescriptions; 2.6% vs 2.4% (AOR, 0.85; 95% CI, 0.77-0.93) for 5 to 19 prescriptions, and 3.2% vs 3.7% (AOR, 0.64; 95% CI, 0.59-0.70) for 20 or more prescriptions. The AORs for current use of statins defined as 20 or more prescriptions were similar (around 0.6) across age, sex, and body mass index categories, and across the statin class.

CONCLUSION

Long-term use of statins was associated with a decreased risk of gallstones followed by cholecystectomy.

摘要

背景

胆结石病是西方国家发病的主要原因之一，且带来高昂的经济负担。他汀类药物可减少肝脏胆固醇的生物合成，因此可能通过降低胆汁中胆固醇浓度来降低胆固醇结石的风险。关于人类中这种关联的数据很少。

目的

研究使用他汀类药物、贝特类药物或其他降脂药物与胆囊切除术后发生胆结石病风险之间的关联。

设计、地点和参与者：使用基于英国的全科医学研究数据库进行病例对照分析。确定了1994年至2008年间的发病患者，并为每位患者匹配4名对照，匹配因素包括年龄、性别、全科医疗、日历时间和在数据库中的病史年限。研究人群中76%为女性，在索引日期时的平均（标准差）年龄为53.4（15.0）岁。使用条件逻辑回归来估计与降脂药物暴露相关的胆囊切除术后发生胆结石的比值比（OR），按暴露时间和持续时间分层。OR值和95%置信区间（CI）针对吸烟、体重指数、缺血性心脏病、中风和雌激素使用情况进行了调整。

主要结局指标

与降脂药物暴露相关的胆囊切除术后发生胆结石病的调整后OR（AOR）。

结果

共确定了27035例胆囊切除术患者和106531例匹配对照，其中包括2396例使用他汀类药物的患者和8868例对照。与未使用相比，当前使用他汀类药物（在疾病首次诊断前90天内记录的最后一次处方）在患者中为1.0%，在对照中为0.8%（AOR，1.10；95%CI，0.95 - 1.27），用于1至4次处方；5至19次处方时分别为2.6%对2.4%（AOR，0.85；95%CI，0.77 - 0.93），20次或更多次处方时分别为3.2%对3.7%（AOR，0.64；95%CI，0.59 - 0.70）。当前使用他汀类药物定义为20次或更多次处方时的AOR在年龄、性别和体重指数类别以及他汀类药物类别中相似（约为0.6）。